OBJECTIVE: To identify the molecular form of GF-6 immunopositive cells in the fetal forebrain. RESULTS We had previously discovered, using antiserum GF-6, two types of LHRH-like neurons, early and late, in fetal forebrains. The late cells arose from the olfactory placode at E32-E36, migrated into the forebrain at E38-E42, and reached the preoptic area and hypothalamus at E50-70. They are bona fide LHRH neurons based on immunostaining with antisera for mammalian LHRH, but not for any other LHRH forms. The origin of early cells was unclear A small number of early cells were seen in the olfactory placode and the forebrain at E30-E32, and a large number of early cells were present in the forebrain at E32-E34. They settled in the extrahypothalamic area (septum, stria terminalis, amygdala, striatum, and internal capsule) at E50-E70, but not in the preoptic area and the hypothalamus. The molecular form of early cells is unknown, since they were not immunostained with any specific antisera against known forms of LHRH. We studied their form using antisera against LHRH1-5 or metalloendopeptidase E.C.3.4.24.15 (EP24.15), an enzyme that cleaves LHRH at the Tyr5-Gly6 position in 9 fetuses at E36 to E70. We found that the late cells were immunostained with antisera GF-6 and LR-1, but not with antisera for LHRH1-5 and EP24.15, while the early cells were readily immunostained with antisera for LHRH1-5 and EP24.15, as well as antiserum GF-6. Exposure of those antisera, preabsorbed with various peptides, revealed that the early cells (extrahypothalamic cells) contain LHRH1-5 and its cleavage enzyme, EP24.15. A group of neurons containing an LHRH1-5 fragment are present in the basal forebrain before the migration of neurons containing full mature LHRH, and they distribute widely in the brain. FUTURE DIRECTIONS We will examine the function of this LHRH fragment in the brain. KEY WORDS LHRH neurons, LHRH fragments, endopeptidase, olfactory placode, fetal brain